Mild Traumatic Brain Injury: Nosology & Pathogenesis

Transcription

1 Psychological Medicine Clinical Academic Group (CAG) Mild Traumatic Brain Injury: Nosology & Pathogenesis Mike Dilley, Lishman Unit, Maudsley Hospital

2 A 38-year-old woman presents to you with a six month history of persistent headache, memory and concentration impairments, irritability, fatigue and sleeplessness. She has not returned to work. Her husband states that all of her difficulties started after a car accident, when her stationary car was shunted from behind. He was with her and is sure that she only lost consciousness for a matter of seconds. Her A&E notes record her GCS as 15, one hour after the accident. She has an Abbreviated Mental Test score of 10/10. Her neurological exam and MRI brain are normal. She wants to know if she has brain damage.

3 HOW SEVERE WAS MY HEAD INJURY? DEFINITIONS OF MTBI

4 Defining Severity Classification of injury severity Depth and duration of loss of consciousness Duration of retrograde and anterograde memory disturbance Glasgow Coma Score (GCS) Teasdale & Jennett 1974 Correlate with survival and major disability but more so in severe injury Rassovsky et al. 2006

5 Problems with defining severity Accurate assessment requires expert observers repeating the measures longitudinally Tate et al Agreement on how to code patients when Sedated, intubated or treated with analgesia Limited assessment in milder injuries Often unwitnessed Consciousness not impaired on arrival to A&E Focus is on serious injuries elsewhere

6 Definitions & Diagnostic Criteria Key definitions and diagnostic criteria for mtbi Centers for Disease Control and Prevention, 2003 World Health Organisation Carroll et al American Congress of Rehabilitation Medicine Kay et al Agree that mtbi can be diagnosed without LOC PTA no longer than 24 hours May or may not have neurological findings Ruff et al. 2009

7 What is mtbi? Glasgow Coma Scale (GCS) Loss of Consciousness < 30 mins Post-traumatic amnesia (PTA) < 24 hours Uncomplicated vs. complicated Approx per 100,000 per annum, but potentially higher Cassidy et al., 2004; Bazarian et al., 2005

8 What is the usual trajectory of post concussion cognitive complaints?

9 In majority of athletes post concussion symptoms are back to baseline by 5 days after a concussion McCrea et al. 2003; Belanger & Vanderploeg, 2005

10 PASAT 4 Score Time course of recovery of Cognitive Impairment: Concussed American footballers compared with controls Mean Test Scores for Injured Players and Student Controls Macciocchi et al Injured Players Controls Paced Auditory Serial Addition Test Percent correct Preseason 24 h after Injury 5 d after Injury 10 d after Injury

11 Can mtbi cause cognitive deficits in acute recovery i.e. up to 3 months? WHO Collaborating Center Task Force on mtbi 428 studies of prognosis; 120 accepted for review Cognitive deficits and symptoms common in acute stage with majority reporting recovery in 3-12 months Consistent and methodologically sound evidence of cognitive deficits in first few days Include problems with recall, speed of information processing and attention Carroll et al., 2004

12 Meta-analysis of Neuropsychological Outcome after mtbi Rohling et al., studies in most recent re-analysis Analysed by epochs of recovery, up to 3 months after injury Identify similar effect sizes over time to previous 4 meta-analyses Larger effect size at T1 (<7 days = -0.39) with little to no effect size at T4 (>93 days = -0.07)

13 Time course of recovery of symptoms Persistent complaints present in 25 65% at 3 months 21 24% at 6 months 14 18% at one year (Jacobson 1995) (a half, a quarter, an eighth at 3, 6, 12 months) At one year 10 20% significant disability (in Glasgow 47% - Thornhill et al., 2000) Ron Ruff s miserable minority

14 I DIDN T HAVE A BRAIN INJURY - I VE HAD A CONCUSSION, DOCTOR DEFINITIONS OF CONCUSSION

15 So what is concussion?...a clinical syndrome characterised by immediate and transient impairment of neural function, such as alteration of consciousness, disturbances of vision, equilibrium, etcetera, due to mechanical forces Caveness and Walker 1966 transient impairment of function as a result of a blow to the brain without LOC; with LOC <1 hour; prolonged LOC ICD-9

16 Classification & Diagnostic Criteria DSM-IV-TR does not define concussion Postconcussional Disorder in research appendix A history of head trauma that has caused significant cerebral concussion. The manifestations of concussion include loss of consciousness, post-traumatic amnesia, and, less commonly, posttraumatic onset of seizures. The specific method of defining this criterion needs to be established by further research Symptom onset following head trauma or otherwise a substantial worsening of preexisting symptoms, lasting for at least 3 months The disturbance causes significant impairment in social or occupational functioning and represents a significant decline from a previous level of functioning. In school-age children the impairment may be manifested by a significant worsening in school or academic performance dating from the trauma.

17 Classification & Diagnostic Criteria International Classification of Diseases, 10 th Edition (ICD-10) defines Postconcussional Syndrome when a patient reports three or more of six symptoms There must be a history of head trauma with LOC The nosological status of this condition is somewhat uncertain Objective EEG, brain imaging or occulonystagmographic evidence for brain damage may be lacking Head trauma precedes symptom onset by up to 4 weeks The complaints are not necessarily associated with compensation motives.

18 Post-concussion Symptoms DSM-IV-TR: Postconcussional Disorder (Research) Neuropsychological test evidence of difficulties: In attention (concentrating, shifting focus of attention, performing simultaneous cognitive tasks) or... With memory (learning or recalling information) Three or more of: Becoming fatigued easily Headache Vertigo or dizziness Irritability or aggression on little or no provocation Anxiety, depression or affective lability Disordered sleep Changes in personality (e.g. social or sexual inappropriateness) Apathy or lack of spontaneity ICD/DCR-10: Postconcussional Disorder (F07.2) Selection of the following (3+ of 1-6): Subjective difficulty in concentrating and performing mental task 1 Subjective impairment of memory 1 Fatigue 2 Headache 2 Dizziness 2 (often lacking features of true vertigo) Irritability 3 Emotional lability, with depression or anxiety 3 Insomnia 4 Reduced tolerance to stress, emotional excitement, of alcohol 5 Preoccupation with symptoms or fear of permanent brain damage 6

19 Early Symptoms Double Vision Blurred vision Nausea Dizziness Drowsiness Insomnia Headache Poor Concentration Noise and light sensitivity Fatigue Irritability Anxiety Depression Late Symptoms

20 Clinical Differences & Diagnostic Validity DSM & ICD PCS identify different populations 40% agreement between diagnostic criteria in a cohort, n = 178 Boake et al But, few differences between symptom or outcome patterns McCauley et al. 2005

21 Post Concussion Symptoms are nonspecific 62 mtbi vs. 58 non-brain injured trauma controls (TC) Post Concussion symptoms variable over time At five days post injury similar rates of Post Concussion symptoms in mtbi (40.3%) vs. TC (50%) Pre-injury depressive or anxiety disorder and acute posttraumatic stress at 5 days most significant predictors of PCS at 3 months Meares et al Overlaps with other disorders such as depression, pain, whiplash, chronic fatigue and somatisation disorders (one disorder or many? Wessely, 2005)

22 Symptoms present in extracranial injury Boake et al And at high rates in the general population Iversen & Lange 2003 mtbi does not predict postconcussion syndrome within a week of the injury Meares et al. 2008

23 Patients aren t sure what concussion is either - 59% have had it, but deny having had a head injury McKinlay et al., 2011

24 And what you call it may matter Concussion vs. mtbi Labeling an injury a concussion strongly predicted earlier discharge from hospital and earlier return to school, in children attending A&E, independent of GCS and the presence of other injuries DeMatteo et al. 2010

25 HAVE I GOT BRAIN DAMAGE? NEUROPATHOLOGICAL EVIDENCE

26 Animal Models Neuropathology in mild injury is qualitatively similar to more severe injury Park et al Axonal injury to subcortical WM, hippocampus, thalamus and cerebellum ranging from stretching to axotomy Farkas & Povlishock 2007 Unclear how animal models represent mtbi in humans

27 Post-mortem studies Post mortems of those who sustain mtbi and die shortly after of other causes 5 patients with minor injury (e.g. no LOC, PTA<30 mins) destruction of myelin, axonal retraction bulbs and aggregation of glial cells Oppenheimer, 1968 APP immunostaining suggests multifocal axonal injury Blumbergs et al. 1994

28 HAVE I GOT BRAIN DAMAGE? NEUROIMAGING EVIDENCE

29 CT CT most commonly used modality 3 large cohort studies assessed abnormal findings in mtbi (GCS 15), n=4000 GCS % abnormal scans GCS 13/ % abnormal scans Borczuk 1995; Haydel et al. 2000; Miller et al Complicated mtbi more likely to be associated with cognitive impairment Iverson, 2006; Lange et al. 2009; Kwok et al. 2008

30 Susceptibility-weighted imaging (SWI) Detects microbleeds in white matter that are not seen on conventional MR sequences But less sensitivity to non-haemorrhagic axonal injury and lack of clarity whether number of microbleeds is related to prognosis In addition to gradient echo can be clinically useful in identifying DAI Sharp et al. 2011

31 White Grey Black controls mtbi moderate / severe TBI On average MRI 9 years post injury Number of ROIs with abnormal anisotropy correlate with executive impairment But, controls also have several ROI that meet criteria Kraus et al., 2007 Overlap with mtbi

32 Working memory task shows increased cerebral blood flow across a wider cortical area than controls, although the task is performed as well as controls, suggesting greater effort required. McAllister et al., 1999

33 WHAT PREDICTS AN INCOMPLETE RECOVERY?

34 Risk Factors Increased age at time of injury regardless of severity Dikmen et al Premorbid psychiatric illness Kashluba et al. 2008; Lange et al Repeated injuries Beaumont et al. 2009; McKee et al. 2009; Rimel et al. 1981

35 Risk Factors: Depression Lange, Iverson et al., 2011 Depression strongly influences post concussion symptom reporting after mtbi vs. depression alone and healthy controls

36 Risk Factors: Attributions & Expectations PCS patients under report normal postconcussion symptoms experienced preinjury the good old days bias Iverson et al Those who expect their injury to have persisting negative consequences have more symptoms at 3 months Whitaker et al. 2007

37 Risk Factors: Attributions & Expectations Hou et al., 2011

38 Risk Factors: Pre-injury Life Events van Veldhoven et al., 2011

39 Compensation - Binder and Rohling 1996 Meta-analysis - closed head injury outcome those with financial incentive vs. those without Effect sizes compared allowed comparison across outcome measures Those with financial incentives have almost half SD more symptoms; equivalent to 25% more symptoms (mean effect size 0.47) Larger effect size the less severe the injury PTA < 1hr = 0.82; PTA > 1hr = 0.28 But, the litigation effect is not consistently reported Hou et al. 2011

40 A way forward for defining PCS? A unified definition of persistent post concussion presentations Acknowledgement of the possibility of a multifactorial aetiology rather than either a brain-based vs. psychological dichotomy Ruff, 2011 proposes a subclassification for DSM IV

41 Ruff, 2011 Four modifiers to DSM IV PCD (TBI + persistent symptoms at 3 months) With neuropathological features Positive neuroimaging Cognitive dysfunction represents brain dysfunction i.e. the complicated-mtbi group

42 With neurocognitive features Negative or unavailable neuroimaging Pre or post-morbid psychological factors do not play a dominant role Evidence of cognitive deficits in attention, memory or executive dysfunction

43 With psychopathological features Negative or unavailable neuroimaging Pre or post-morbid cognitive factors do not play a dominant role With mixed features